The overarching mission of this comprehensive All In DIPG initiative is two-fold: 1) to establish and maintain a major effort to coordinate DIPG studies in order to more efficiently and successfully advance therapeutics for DIPG, and 2) to establish a critical pipeline of therapeutic trials for all stages of the DIPG disease process. The vision is of a public-private partnership for multi-investigator, multi-site collaborative efforts led by the NCI. It calls for intramural and extramural research projects and engages non-profit organizations, the government and pharmaceutical companies. High-throughput screening of large collections of compounds can identify and help prioritize drug candidates. Knowledge of tumor cell sensitivity, however, is insufficient predictor of success in the clinic. A compound must reach the tumor in the CNS, it must be present at the tumor site in effective concentrations and for a sufficient period of time, the drug's molecular target must be present (if it's a targeted therapy) and treatment must have an acceptable side effect profile. The preclinical scope of All In covers these parameters. Research on DIPG is performed in laboratories throughout the world, but it is highly fragmented and efforts are not coordinated. Very rarely does a single lab identify a targeted agent, study its pharmacokinetics and assess its pharmacodynamic effects. When a drug enters the clinic, there are often significant gaps in its preclinical profile and differences in results or data interpretation remain unreconciled. For a drug to meet with clinical success many biological factors beyond sensitivity of tumor cells come into play. Fortunately, it is now possible to study and determine these critical drug parameters experimentally in the laboratory /preclinical setting. However, it can be very difficult to get funding for expanding preclinical testing to fill these informational gaps. Thus, a comprehensive paradigm that helps ensure sufficient preclinical data are obtained and eliminates duplication of effort is needed. More extensive preclinical evaluation will strengthen scientific rationale and likely improve the efficiency and success of clinical trials for children with DIPG. The goals and objectives are; to strengthen DIPG disease-specific pre-clinical therapeutic rationale through high throughput drug screens on appropriate cell lines, translation and validation in appropriate in vivo models, identification of effective exposure, characterization of CNS pharmacokinetics, and early comprehensive clinical trials on a limited number of patients for validation prior to extending to larger efficacy studies. Goals for a specific therapy in development will be defined, preclinical informational gaps will be assessed and methods to address them will be undertaken. For example, establish biologically effective dose, conduct drug delivery studies in non-human primates, cross-validation of PK studies in the CSF and the brain, establish reproducibility of results in various models. In some cases, next steps may include conducting parallel early phase 0/1 studies in small numbers of patients. Thus, All In also includes a clinical component. Six participating sites have been identified: Lurie Children's, NCI, Seattle Children's, Stanford University, Texas Children's, and the University of Florida in Gainesville. The clinical aims are to expand and enhance this DIPG-focused clinical consortium infrastructure and allow continued translational evaluations of promising therapeutics.